Anaphylaxis is a severe allergic reaction that can be rapidly progressing and fatal; thus, establishing the etiology of anaphylaxis is pivotal to long-term risk management.
Alpha-gal syndrome is a recently identified type of food allergy to red meat. In the United States, the condition most often begins when a Lone Star tick bite transmits a sugar molecule called alpha-gal into the body. In some people, this triggers an immune system reaction that later produces mild to severe allergic reactions when they eat red meat.
The research.…..Hypersensitivity in the allergic setting refers to immune reactions, stimulated by soluble antigens, that can be rapidly progressing and in the case of anaphylaxis are occasionally fatal. As the number of known exposures associated with anaphylaxis is limited, identification of novel causative agents is important in facilitating both education and other allergen-specific approaches that are crucial to long-term risk management. Within the last 10 years, several seemingly separate observations were recognized to be related, all of which resulted from the development of antibodies to a carbohydrate moiety on proteins where exposure differed from airborne allergens but which were nevertheless capable of producing anaphylactic and hypersensitivity reactions.
Our recent work has identified these responses as being due to a novel IgE antibody (Ab) directed against a mammalian oligosaccharide epitope, galactose-alpha-1,3-galactose (alpha-gal) 1. This review will present the history and biology of alpha-gal and discuss the evidence that the IgE response to alpha-gal is different from typical IgE responses directed towards protein allergens.
Early work by Karl Landsteiner discovered that all humans had antibodies to a blood group “B-like” oligosaccharide found on non-primate red blood cells5. That antigen was subsequently identified as galactose-alpha-1,3-galactose (alpha-gal) and represents a major transplantation barrier between primates and other mammals.
Antibodies against alpha-gal are present in all non-immunocompromised human subjects and some early studies suggested that the IgG antibodies against alpha-gal constituted about 1% of circulating immunoglobulins in human subjects, apes, and Old World monkeys 9. Recent work in our lab with specific assays for IgG antibodies suggests that the percentages are not this high. As discussed below, the fact that all non-primate mammals including mice can make oligosaccharides that are foreign to humans is an important component of our story.
The Red Meat Connection
Between 2006 – 2008, a number of patients were evaluated, most of whom spent a significant amount of time outdoors, who had presented with episodes of generalized urticaria, angioedema or recurrent anaphylaxis.
The importance of the time spent outdoors was not clear at that time.
There was no obvious immediate cause for the symptoms, but in several cases the patients reported that they felt the reactions might be due to consumption of meat 3–5 hours earlier.
Prick tests were performed with commercial extracts of beef, pork or lamb, and produced small wheals only 2– 4 mm in diameter that often would be interpreted as negative.
Analysis was done to determine why these people were having a reaction to red meat. The testing was intradermal skin testing with commercial meat extracts or prick skin tests with fresh meat extracts both of which demonstrated strong positive results.
These results were confirmed with blood tests for specific IgE Ab to red meats.
These results were popping up across the southeast and yet no formal studies were or had been conducted…
Starting in 1989, Mrs. Sandra Latimer together with Dr. Antony Deutsch from Athens, Georgia collected ten cases of delayed reactions to mammalian meat and made a connection with the occurrence of tick bites several weeks or months prior to the first episode of hives or anaphylaxis. They presented these findings to the Georgia Allergy Society and to the CDC in 1991, but no additional reports or statements were issued by either of these organizations.
The characteristics of red meat allergy are different from typical allergic reactions. Common complaints include both gastrointestinal symptoms and urticaria, but unlike most allergic reactions, patients do not develop any symptoms for until after at least 2 hours after eating red meat, while many reactions are delayed for 3–5 hours or even longer.
Nonetheless, symptoms can be severe or even life threatening.
Many of the patients described nausea, diarrhea or indigestion before a reaction, however the most common symptom reported was itching. The presence of symptoms before a severe reaction is common, but not a requirement. Many patients do not have any symptoms and even those who have had them previously, the symptoms do not occur with every exposure to red meat. All of the patients had consumed red meat without complications for many years prior to the onset of the syndrome. While some individuals had a prior history of allergy, most of the cases had no previous allergic symptoms, thus an atopic disposition does not appear to predispose patients to this kind of IgE response.
Three observations led to the investigation of whether IgE antibodies to alpha-gal were present in the sera of adult patients reporting reactions to beef. Alpha-gal is known to be present on both tissues and meat from non-primate mammals 15, the antibodies causing reactions to cetuximab were directed against alpha-gal, and the geographical distribution of the reactions to cetuximab overlapped the same geographical area where the red meat reactions were occurring.
Not surprisingly, the patients’ sera tested positive for IgE to beef, pork, lamb, cat and dog, but not to non-mammalian meat such as turkey, fish or chicken.
The presence of alpha-gal was confirmed using two different absorption assays, one with alpha-gal on human serum albumin and the other using thyroglobulin, which is heavily decorated with alpha-gal. The glycosylated antigens were bound to sepharose beads 14. In each case, the specific IgE binding to beef, pork, lamb, cat and dog was reduced by >75%.
This is the latest map of lone star tick locations, HOWEVER— this map is outdated. These ticks have been found as far west as New Mexico (as of last year 2017).
Given that tick bites represent the most important cause of alpha-gal sensitization in USA, Sydney, and Stockholm, why has our recognition of this problem increased so dramatically over the past 10 years?
The increase in Lone Star ticks parallels the increase in the deer population, a major carrier of these ticks, throughout the United States over the last 30–40 yrs 23, 24 making it more likely that people who walk in the woods or in long grass will be bitten at some point.
The increasing deer population can also be linked to the enactment of leash laws for dogs, a decrease in the number of hunters and movement of the deer into suburban areas. This last point is important as the deer provide a means for the ticks to be transported over large geographic areas quickly.
Clearly, the increase in tick exposure is one plausible explanation for the increase in the number of cases. However, the data from different countries demonstrate that not all tick bite per se or a tick bite from one particular species result in the problem.
Signs and symptoms of an alpha-gal allergic reaction are often delayed compared with other food allergies. Most reactions to common food allergens — peanuts or shellfish, for example — happen within minutes of exposure. In alpha-gal syndrome, signs and symptoms typically don’t appear for three to six hours after eating red meat.
Signs and symptoms of alpha-gal syndrome may include:
Hives, itching, or itchy, scaly skin (eczema)
Swelling of the lips, face, tongue and throat, or other body parts
Wheezing or shortness of breath
A runny nose
Abdominal pain, diarrhea, nausea or vomiting
Anaphylaxis, a severe, potentially deadly allergic reaction that restricts breathing
Doctors think the time delay between eating red meat and developing an allergic reaction is one reason the condition was overlooked until recently: A possible connection between a T-bone steak with dinner and hives at midnight was far from obvious.
So the real question is……..
WHY DO WE SUDDENLY HAVE ALL OF THESE NEW DISEASES..?
Were they always around and no one knew?
Are they engineered ??
Are they a result of environmental changes, pollution, and our global interconnectedness???
However they came about, there is real concern. Ticks spread a variety of bacteria and viruses. There are new ones being discovered everyday. (or every year…lol)